US4956128A
Expired / Lapsed
US
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Droplet generation
Assignee: Sanofi Pasteur Ltd
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Filing: 1986-11-13
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Granted: 1990-09-11
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Expires: 2006-11-13
Abstract
Abstract Perfectly spherical, smooth and uniform microcapsules, which may contain living cells, are produced having a diameter less than 700 μm by employing an electrostatic droplet generator. A droplet is suspended from a pointed source, such as a needle, and is charged with high static voltage. A collecting vessel or ring device is charged with opposing polarity and attracts the droplet. When a voltage potential threshold is passed, the droplet moves from the source to the collecting vessel. The voltage pulse height, pulse frequency and length, and extrusion rate of the droplets are adjustable so that predetermined sizes of droplets may be repeatedly generated and collected.
Inventors
- 👤 Martin Hommel
- 👤 Anthony M. Sun
- 👤 Mattheus F. A. Goosen
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 17:05
CPC Classifications
C; C12; C12N; C12N11/00; C12N11/02; C12N11/04; A; A61; A61F; A61F2/00; A61F2/02; A61F2/022; A61K; A61K35/00; A61K35/12; A61K35/37; A61K35/39; A61K9/00; A61K9/14; A61K9/16; A61K9/1605; A61K9/1629; A61K9/1652; A61K9/48; A61K9/50; A61K9/5005; A61K9/5021; A61K9/5026; A61K9/5031; A61K9/5073; A61L; A61L27/00; A61L27/14; A61L27/20; A61L27/36; A61L27/38; B; B29; B29B; B29B9/00; B29B9/10; G; G01; G01N; G01N15/00; G01N15/10; G01N15/14; G01N15/149
Claims Analysis
Total Claims: 17
Claim 1
Independent Claim
275 words
A method of forming spherical, smooth and uniform microapsules containing living tissue or cells, which comprises: forming a suspension of living tissue or cells in a physiologically-compatible medium containing a water-soluble substance which can be reversibly gelled to provide a temporary protective environment for the living tissue or cells, extruding said suspension downwardly from a source at a first location comprising an axially downwardly directed electroconductive needle, charging the extruded material with a charge of one polarity, establishing a charge of opposite polarity at a second location spaced vertically below said first location, providing a difference in voltage between the first location and second location cyclically in pulses of a magnitude from about 1 to about 25 kv at a frequency of about 10 to about 100 sec-1 for a pulse duration of about 1 to about 6 m. sec. to effect continuous production of droplets from the extruded material and to draw the droplets so-formed towards said second location, collecting said droplets in a recipient medium which is a hardening solution which reacts with said water-soluble substance and form discrete, spherical microcapsules from each of said droplets of diameter less than about 700 microns, and subsequently forming a permanent biocompatible semi-permeable membrane having a negatively-charged outer surface about each of said microcapsules which forms a core of the resulting spherical, smooth and uniform microcapsules, said membrane permitting nutrients and oxygen to flow to the core material and metabolic products to flow therefrom while retaining the core material within the microcapsule, said membrane comprising ionically-interacted biocompatible materials and having a thickness about 4 to about 6 microns, said resulting microcapsules being suitable for cardiovascular injection.
Claim 2
Independent Claim
275 words
A method of forming spherical, smooth and uniform microapsules containing living tissue or cells, which comprises: forming a suspension of living tissue or cells in a physiologically-compatible medium containing a water-soluble substance which can be reversibly gelled to provide a temporary protective environment for the living tissue or cells, extruding said suspension downwardly from a source at a first location comprising an axially downwardly directed electroconductive needle, charging the extruded material with a charge of one polarity, establishing a charge of opposite polarity at a second location spaced vertically below said first location, providing a difference in voltage between the first location and second location cyclically in pulses of a magnitude from about 1 to about 25 kv at a frequency of about 10 to about 100 sec-1 for a pulse duration of about 1 to about 6 m. sec. to effect continuous production of droplets from the extruded material and to draw the droplets so-formed towards said second location, collecting said droplets in a recipient medium which is a hardening solution which reacts with said water-soluble substance and form discrete, spherical microcapsules from each of said droplets of diameter less than about 700 microns, and subsequently forming a permanent biocompatible semi-permeable membrane having a negatively-charged outer surface about each of said microcapsules which forms a core of the resulting spherical, smooth and uniform microcapsules, said membrane permitting nutrients and oxygen to flow to the core material and metabolic products to flow therefrom while retaining the core material within the microcapsule, said membrane comprising ionically-interacted biocompatible materials and having a thickness about 4 to about 6 microns, said resulting microcapsules being suitable for cardiovascular injection.
Claim 3
Dependent Claim
15 words
The method of claim 1 wherein said recipient medium is provided at said second location.
Claim 4
Dependent Claim
36 words
The method of claim 1 when said second location comprises a ring of electroconductive material surrounding the axis of said needle and being concentric to said axis and such recipient medium is location below said location.
Claim 5
Dependent Claim
14 words
The method of claim 1 wherein said water-soluble substance is a gellable polysaccharide gum.
Claim 6
Dependent Claim
11 words
The method of claim 4 wherein said polysaccharide-gum is sodium alginate.
Claim 7
Dependent Claim
15 words
The method of claim 1 wherein said hardening solution comprises an aqueous calcium chloride solution.
Claim 8
Dependent Claim
37 words
The method of claim 6 wherein said semi-permeable membrane is formed about each of the microcapsules by ionic reaction between free acid groups in the surface layer of the gelled gum and biocompatible polymers containing acid-reactive groups.
Claim 9
Dependent Claim
13 words
The method of claim 7 wherein said biocompatible polymer is a polyamino acid.
Claim 10
Dependent Claim
21 words
The method of claim 8 wherein said polyamino acid is polylysine having a molecular weight of about 10,000 to about 30,000.
Claim 11
Dependent Claim
18 words
The method of claim 9 wherein said polylysine is reacted with the microcapsules for at least six minutes.
Claim 12
Dependent Claim
41 words
The method of claim 7 where said biocompatible polymers, after reaction with the gelled gum, is treated with a non-toxic biocompatible water-soluble polymeric materials capable of ionic reaction with free amino groups to form an outer negatively-charged coating about the membrane.
Claim 13
Dependent Claim
14 words
The method of claim 11 wherein said water-soluble polymer material is a polysaccharide gum.
Claim 14
Dependent Claim
11 words
Themethod of claim 12 wherein said polysaccharide gum is sodium alginate.
Claim 15
Dependent Claim
10 words
The method of claim 1 including reliquifying the core material.
Claim 16
Dependent Claim
27 words
The method of claim 1 wherein said living tissue is islets of Langerhans, whereby said cardiovascular injection permits control of blood sugar levels in an animal body.
Claim 17
Dependent Claim
18 words
The method of claim 1 wherein said microcapsules have a diameter of about 150 to about 500 microns.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1993-09-10 | 1994-03-12 | 1994-09-11 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1997-09-10 | 1998-03-12 | 1998-09-11 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2001-09-10 | 2002-03-12 | 2002-09-11 | $7700.00 | Window Closed / Lapsed |